Project Summary/Abstract The Research Plan describes two experiments that will examine how spatial information is processed in the mammalian brain ? particularly in regards to navigation in three-dimensional (3-D) space. Previous studies have identified a population of neurons, referred to as head direction cells, that discharge as a function of the animal?s directional heading in the horizontal plane. HD cells have primarily been recorded in two-dimensional space. Different theories have postulated how they respond in 3-D space. Aim 1 will test these theories by recording HD cells as an animal locomotes different routes on the surface of a 3-D cube. In particular, we will determine whether cell firing is comutative as the animal travels different routes from the floor up the vertical walls to the top surface. Each theory makes different predictions as how the cells will fire when the animal reaches the top surface. A second spatial cell type are grid cells in the entorhinal cortex. These cells fire when the animal is at multiple locations; the locations form a regular, repeating hexagonal pattern that forms a grid. Aim 2 will assess how grid cells fire across two horizontal planes that occupy the same location in the environment, but are offset in the vertical plane. We will determine if the grid patterns between the two surfaces are in alignment or offset from one another. Knowing how grid cells respond under these conditions has important implications for understanding how the grid cell signal is generated. In sum, these studies will provide insight into how 3-D spatial information is organized and processed in the brain and will enhance our understanding of the functional role of HD and grid cells during navigation. The results have implications for human health and behavior. It is common for patients with vestibular disorders and patients with Alzheimer?s disease, a disease often associated with marked pathology in limbic system structures, to experience spatial disorientation to the extent that constant supervision is required. Learning how spatial information is processed in the rat brain will give us clues about the complex nature of spatial processes in humans.